A potential of propolis on major virulence factors of Cryptococcus neoformans

Thammasit, Patcharin; Iadnut, Anupon; Mamoon, Ketsaya; Khacha-ananda, Supakit; Chupradit, Koollawat; Tayapiwatana, Chatchai; Kasinrerk, Watchara; Tragoolpua, Yingmanee; Tragoolpua, Khajornsak

doi:10.1016/j.micpath.2018.07.028

Cited by 17 publications

(15 citation statements)

References 36 publications

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“…One main problem in getting efficient remedies comes from the intrinsic resistance of C. neoformans to echinocandins, due to its very low β-glucan content in the cell wall [ 6 , 7 ]. Furthermore, C. neoformans contains other exclusive features of virulence, such as an external polysaccharide capsule [ 7 , 8 ] and the capacity to synthesize melanin in growth media containing diphenolic compounds, such as catecholamines, which are present in the nervous system of infected patients [ 9 ]. Melanin is able to absorb and bind a number of drugs in polyphenolic polymer, including polyenes, diminishing the actual doses and efficacy of those treatments in the fungal cells.…”

Section: Introductionmentioning

confidence: 99%

A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans

Argüelles¹,

Sánchez-Fresneda

Martínez-Mármol

et al. 2021

Antibiotics

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Current antifungal chemotherapy against the prevalent basidiomycete Cryptococcus neoformans displays some drawbacks. This pathogenic fungus is refractory to echinocandins, whereas conventional treatment with amphotericin B plus 5-fluorocytosine has a limited efficacy. In this study, we explored the potential cryptococcal activity of some natural agents. After conducting a screening test with a set of propolis from different geographical areas, we selected an extract from China, which displayed a certain cytotoxic activity against C. neoformans, due to this extract being cheap and easily available in large amounts. The combination of this kind of propolis with carnosic acid in a 1:4 ratio induced a stronger fungicidal effect, which occurred following a synergistic pattern, without visible alterations in external cell morphology. Furthermore, several carnosic acid–propolis formulations applied onto preformed biofilms decreased the metabolic activity of the sessile cells forming biofilms. These data support the potential application of mixtures containing these two natural extracts in the design of new antifungal strategies in order to combat opportunistic infections caused by prevalent pathogenic fungi.

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Section: Introductionmentioning

confidence: 99%

A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans

Argüelles¹,

Sánchez-Fresneda

Martínez-Mármol

et al. 2021

Antibiotics

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“…In vivo treatment of G. mellonella larvae infected with C. neoformans with propolis-loaded PBCA-NP showed that these nanoparticles significantly prolonged the survival of the infected larvae, an invertebrate host. This action can be attributed to the ability of propolis to inhibit the growth and virulence factors of cryptococcal cells as shown in vitro (Thammasit et al, 2018). Although testing in G. mellonella is unlikely to fully replace toxicity testing in mammals, it is a convenient step between in vitro tests and testing in mammals (Ignasiak and Maxwell, 2017), allowing to reduce to a minimum classical animal experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Gallic acid, quercitin, pinocembrin, chrysin, and galangin were found in the ethanol extract of our propolis samples that are responsible for its biological and pharmaceutical properties ( Torres et al, 2018 ). We found that the high efficacy of sub-MIC (ranging from 0.5 to 0.125 mg/ml) of ethanol extract of propolis possessed the ability to decrease cryptococcal virulence factors ( Thammasit et al, 2018 ). Although extraction with ethanol is suitable for revealing the mode of propolis against fungal virulence factors, it has some limitations of application because of its scarce solubility in water.…”

Section: Introductionmentioning

confidence: 99%

Targeted Propolis-Loaded Poly (Butyl) Cyanoacrylate Nanoparticles: An Alternative Drug Delivery Tool for the Treatment of Cryptococcal Meningitis

et al. 2021

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In this study, we describe a nano-carrier system for propolis that is able to cross an in vitro model of the blood-brain barrier (BBB) and effectively reduce the virulence of Cryptococcus neoformans in animal models. Antimicrobial properties of propolis have been widely studied. However, propolis applications are limited by its low water solubility and poor bioavailability. Therefore, we recently formulated novel poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NP) containing propolis. PBCA-NP are biocompatible, biodegradable and have been shown to effectively cross the BBB using apolipoprotein E (ApoE) as a ligand. Prepared nanoparticles were characterized for particle size, zeta potential, propolis entrapment efficiency and in vitro release. Additionally, the PBCA-NP were functionalized with polysorbate 80, which then specifically adsorbs ApoE. Using an in vitro BBB model of human brain microvascular endothelial cells hCMEC/D3, it was shown that fluorescence labelled ApoE-functionalized PBCA-NP were internalized by the cells and translocated across the cell monolayer. Propolis-loaded PBCA-NP had in vitro, antifungal activity against C. neoformans, which causes meningitis. To utilize the invertebrate model, Galleria mellonella larvae were infected with C. neoformans and treated with propolis-loaded PBCA-NP. The larvae exhibited normal behavior in toxicity testing, and treatment with propolis-loaded PBCA-NP increased survival in the C. neoformans-infected larvae group. In addition, following cryptococcal infection and then 7 days of treatment, the tissue fungal burden of mice treated with propolis-loaded PBCA-NP was significantly lower than control groups. Therefore, our ApoE-functionalized propolis-loaded PBCA-NP can be deemed as a potential targeted nanoparticle in the therapeutic treatment of cerebral cryptococcosis.

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“…Sanpa et al demonstrated that the stingless bee (SLB) propolis ( Tetragonula laeviceps ) inhibited the growth of Staphylococcus epidermidis [ 12 ]. Recently, Thammasit et al reported the potential of propolis from Apis mellifera to decrease the major virulence factors of C. neoformans [ 13 ]. However, the effect of SLB propolis interfering with cell wall-associated melanin retention in the cell wall of C. neoformans , and the immune responses of phagocytes in the defense against SLB propolis-treated yeast infections, has not been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Properties of Thai Stingless Bee Propolis via Diminishing Cell Wall-Associated Cryptococcal Melanin and Enhancing the Fungicidal Activity of Macrophages

et al. 2020

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Cryptococcus neoformans, a life-threatening human yeast pathogen, has the ability to produce melanin, which is one of the common virulence factors contributing to cryptococcal pathogenesis. This virulence factor is closely associated with the cryptococcal cell wall, specifically chitin and chitosan polysaccharides, a complex structure that is essential for maintaining cellular structure and integrity. In this study, we aim to investigate the effects of two stingless bee (SLB) propolis from Tetragonula laeviceps and Tetrigona melanoleuca against cell wall-associated melanin in C. neoformans, and its immune response in RAW 264.7 macrophage. The ethanolic extract of SLB propolis (EEP) has strongly exhibited anti-cryptococcal activity. Moreover, EEP from both sources reduced chitin/chitosan and melanin production against C. neoformans in a dose-dependent manner. Likewise, the mRNA expression level of CDA1, IPC1-PKC1 and LAC1 genes involved in the cryptococcal melanization pathway was significantly decreased at 2 mg/mL in EEP treatment. Additionally, pretreatment with EEP prior to yeast infection dramatically reduced intracellular replication of C. neoformans in RAW 264.7 macrophages in a dose-dependent manner. This study might be a new insight to use a natural powerful source, not only acting to target cell wall-associated molecules, but also being capable to explore a novel strategy by which dysregulation of these molecules leads to promote immunomodulatory activity.

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A potential of propolis on major virulence factors of Cryptococcus neoformans

Cited by 17 publications

References 36 publications

A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans

A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans

Targeted Propolis-Loaded Poly (Butyl) Cyanoacrylate Nanoparticles: An Alternative Drug Delivery Tool for the Treatment of Cryptococcal Meningitis

Unveiling the Properties of Thai Stingless Bee Propolis via Diminishing Cell Wall-Associated Cryptococcal Melanin and Enhancing the Fungicidal Activity of Macrophages

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